Enantioselective synthesis alkaloids

The wM-diacetate 363 can be transformed into either enantiomer of the 4-substituted 2-cyclohexen-l-ol 364 via the enzymatic hydrolysis. By changing the relative reactivity of the allylic leaving groups (acetate and the more reactive carbonate), either enantiomer of 4-substituted cyclohexenyl acetate is accessible by choice. Then the enantioselective synthesis of (7 )- and (S)-5-substituted 1,3-cyclohexadienes 365 and 367 can be achieved. The Pd(II)-cat-alyzed acetoxylactonization of the diene acids affords the lactones 366 and 368 of different stereochemistry[310]. The tropane alkaloid skeletons 370 and 371 have been constructed based on this chemoselective Pd-catalyzed reactions of 6-benzyloxy-l,3-cycloheptadiene (369)[311]. 

The Pictet-Spengler condensation has been of vital importance in the synthesis of numerous P-carboline and isoquinoline compounds in addition to its use in the formation of alkaloid natural products of complex structure. A tandem retro-aldol and Pictet-Spengler sequence was utilized in a concise and enantioselective synthesis of 18-pseudoyohimbone. Amine 49 cyclized under acidic conditions to give the condensation product 50 in good yield. Deprotection of the ketone produced the indole alkaloid 51. 

The high enantioselectivity of the exo product opens up a new and readily accessible route to an enantioselective synthesis of interesting isoquinoline alkaloids (Scheme 6.15) [35]. The tricyclic isoxazolidine exo-15b was obtained from the 1,3-dipolar cydoaddition reaction as the pure exo isomer and with 58% ee [34]. As shown in Scheme 6.15 the exo product from the 1,3-dipolar cydoaddition was converted into 17 in two steps without racemization at the chiral center. In addition to the illustrated synthesis, the 6,7-dimethoxy-derived isoxazolidine exo-15b is a very useful precursor for the synthesis of naturally occurring isoquinoline alkaloids [36-40]. 

An application of this method is the enantioselective synthesis of harmonine, a defence alkaloid of ladybugs9. The conversion of hydrazines to the corresponding carbamates is advantageous for two reasons ... 

Scheme 10.12 gives some examples of enantioselective cyclopropanations. Entry 1 uses the W.s-/-butyloxazoline (BOX) catalyst. The catalytic cyclopropanation in Entry 2 achieves both stereo- and enantioselectivity. The electronic effect of the catalysts (see p. 926) directs the alkoxy-substituted ring trans to the ester substituent (87 13 ratio), and very high enantioselectivity was observed. Entry 3 also used the /-butyl -BOX catalyst. The product was used in an enantioselective synthesis of the alkaloid quebrachamine. Entry 4 is an example of enantioselective methylene transfer using the tartrate-derived dioxaborolane catalyst (see p. 920). Entry 5 used the Rh2[5(X)-MePY]4... 

Another example of this useful domino process is the enantioselective synthesis of the quinozilidine alkaloid (-)-lasubine II [234]. Condensed tricyclic compounds as 6/3-28 can also be prepared from norbomene derivatives 6/3-27 in excellent yield, as shown by Funel and coworkers (Scheme 6/3.6) [235]. 

B. Lygo, P. G. Wainwright, A New Class of Asymmetric Phase-Transfer Catalysts Derived from Cinchona Alkaloids - Application in the Enantioselective Synthesis of a-Amino Acids , Tetrahedron Lett., 1997, 38, 8595-8598. 

Adults of the Steninae possess paired eversible abdominal defensive gland reservoirs [119,128]. When the beetles walk on the water surface the spreading secretion propels the beetle forward which represents an unique escape mechanism. The secretion contains isopiperitenole 57,1,8-cineole 58,6-methyl-5-hepten-2-one and the unique spreading alkaloid stenusine, N-ethyl-3-(2-methylbutyl)piperidine 59. Natural stenusine was found to be a mixture of all four stereoisomers in a ratio of (S, S) (S, R) (R, R) (R, S)=43 40 13 4. An enantioselective synthesis of stenusine has been carried out via an Enders-approach [129]. 

Cha and co-workers (50) reported a short enantioselective synthesis of the indo-lizidine alkaloid, (—)-swainsonine (247) involving an intramolecular cycloaddition... 

First Enantioselective Synthesis of Dendrobatid Alkaloids Indolizidine 2091 and 223J 53... 

A formal enantioselective synthesis of (-)-bninsvigine (416) was also available by O-debenzylation and O-desilylation of 485 to the known triol 425, the racemic form of which had been utilised in the preparation of the ( )-alkaloid by Hoshino etal [105] (vide supra). 

Recently, Mukaiyama and co-workers prepared cinchona alkaloid-derived chiral quaternary ammonium phenoxide-phenol complex 23 and used it as an efficient organocatalyst for the tandem Michael addition and lactonization between oc,f-unsaturated ketones and a ketene silyl acetal 24 derived from phenyl isobutyrate. This approach permits the highly enantioselective synthesis of a series of 3,4-dihydropyran-2-ones (25), as shown in Scheme 4.11 [17]. 

Decahydroquinoline Alkaloids.—Full details of an earlier briefly described synthesis of ( )-pumiliotoxin C have been published.28 Other total syntheses of the same compound have been documented, starting from trans-4-hexenal,29 and from ethyl tra s-buta-l,3-diene-l-carbamate.30 An enantioselective synthesis of natural (-)-pumiliotoxin-C hydrochloride (34) has also been described (Scheme 6),... 

The enantioselective synthesis of (-)-sedacryptine, a piperidine alkaloid, has been achieved via the double intramolecular conjugate addition of a carbamate group onto a vinyl sulfone and then an enone (Scheme 30). The first conjugate addition of 108 proceeded in a. syn-1,3 fashion. The successive cyclization of the resulting carbamate anion 110, which was formed from carbanion 109 via proton transfer, gave a mixture of stereoisomeric products 111 and 112. Both of these isomers were converted into the target natural product.76... 

A novel Pd-catalyzed asymmetric annulation was reported between 5-bromopyrrole-2-carboxylate esters and vinyl aziridines <07OL2357>. The resulting pyrrolopiperazinones such as 58 served as key intermediates in the enantioselective synthesis of longamide B and a number of other pyrrole alkaloids. 

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